A recent case series reported the incidental findings of improved social and language skills after the administration of the drug Secretin in patients with autistic spectrum disorders (Horvath et al., 1998). The researchers reported that three children who underwent upper gastrointestinal endoscopy and intravenous administration of Secretin demonstrated notable amelioration in gastrointestinal symptoms, as well as significant improvement in their social and language behavior. The findings suggest an association between gastrointestinal and neuropsychological functioning. The present pilot study is designed to investigate the effect of Secretin therapy on autistic subjects through a 16 week, double-blind, placebo controlled cross-over study on a group of autistic subjects stratified by the presence or absence of gastrointestinal symptoms. Unlike the initial study discussed above, the subjects will be assessed using state-of-the-art diagnostic instruments, undergo a comprehensive neuropsychological assessment, and receive objective measures before and after treatment. The comprehensive investigation requires a center which is designed to facilitate the repeated, multidimensional analyses necessary, such as the GCRC. The study involves multiple visits and evaluations by research team members from neuropsychology, neurology, gastrointerology and speech and communication.